Reviving 'tired' immune cells gives blood cancer treatment a boost

UK researchers have discovered a way of improving the effectiveness of bone marrow transplantation, a key treatment for many patients with blood cancer, by providing an extra ‘boost’ to the immune system.

Each year in the UK, over 1000 patients receive blood or bone marrow transplants from a healthy donor as treatment for leukaemia or lymphoma. This therapy not only provides the patient with a new bone marrow but also a new immune system. This means that immune cells from the donor can attack the blood cancer, known as the ‘graft-versus-leukaemia’ effect. Killing residual blood cancer cells is a critical part of the transplant process and is almost certainly necessary to achieve a cure.

The researchers from the University College London, together with collaborators at Harvard and Columbia Universities in the United States, examined why blood cancers come back in some patients who receive a transplant. In a study funded by Leukaemia & Lymphoma Research, and published online in the Journal Of Clinical Investigation, the scientists showed that cancer-targeting immune cells can become ‘worn out’ and stop working. This means that the graft-versus-leukaemia effect may be lost. Importantly, a new treatment can revive the ‘tired’ immune cells and get them to start working again.

By using clinically relevant mouse models of bone marrow transplantation, the researchers found that normal tissues outside the bone marrow were responsible for causing ‘exhaustion’ of the immune cells. This occurred because the normal cells have a molecule on their surface that eventually switches off the immune cells. They went on to show that treatment with an antibody could block this molecule and re-invigorate the immune system. Importantly, this could be done safely without any harmful side effects.

Dr. Ronjon Chakraverty, a bone marrow transplant physician at University College London who led the research team, said: ‘We have known for some time about the existence of the graft-versus-leukaemia response, but we didn’t understand why sometimes it doesn’t last. Our research helps to explain this failure and offers the potential of a new strategy to treat or prevent relapse of blood cancer in patients following bone marrow transplantation.’

Professor David Linch of the Cancer Institute at University College London, said: ‘These are exciting results, not only explaining why treatment may fail in some patients, but also paving the way towards improved therapy.’

Dr. David Grant, Scientific Director at Leukaemia & Lymphoma Research, said: ‘The more we understand about why bone marrow transplants can cure some patients but not others, the more we can use this form of treatment in the most effective way possible. This is a key discovery which will prevent many patients relapsing in the future.’